Compound independent calibration (CIC) can be used to measure stable isotopically labeled molecules and their metabolites. This study was designed to demonstrate that gas chromatography coupled to atomic emission detection and CIC are useful analytical tools for the specific and quantitative determination of13C and15N labeled caffeine and its metabolites. These labeled compounds can be measured by monitoring either13C or15N atomic emission lines and using only one calibration function from one of the analytes. This method can be helpful when it is difficult or impossible to obtain an authentic reference material, which is often the case in metabolic studies.